Hepatobiliary System

Liver, Oval Cell - Hyperplasia

Narrative

Comment:

Oval cell hyperplasia (Figure 1) is rarely seen in control animals. It typically begins either in periportal areas or in subcapsular regions of the liver. The proliferating oval cells are spindloid and initially extend out from portal areas in a linear array; they may encircle hepatic lobules, and in severe cases they may form irregular solid nests of proliferating cells. Since oval cell hyperplasia occurs primarily in animals treated with hepatotoxic xenobiotics or in cases of infection, it is usually associated with varying degrees of hepatocyte degeneration and necrosis and bile duct hyperplasia. Figure 1 was graded as 2+ (mild), and Figure 2, Figure 3, and Figure 4 as 4+ (marked).

Recommendations:

Oval cell hyperplasia should be diagnosed and given a severity grade whenever present, even when part of a complex set of hepatic changes. The pattern and extent of oval cell hyperplasia should be described in the pathology narrative along with accompanying hepatic changes.

References:

Cattley RC, Popp JA. 2002. Liver. In: Handbook of Toxicologic Pathology (Haschek WM, Rousseaux CG, Wallig MA, eds). Academic Press, San Diego, 2:187-225.

Eustis SL, Boorman GA, Harada T, Popp JA. 1990. Liver. In: Pathology of the Fischer Rat (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 71-94.

Evans JG, Lake BG. 1998. The digestive system II. Hepatobiliary system. In: Target Organ Pathology (Turton J, Hooson J, eds). Taylor and Francis, London, 61-98.

Greaves P. 2007. Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation, 3rd ed. Elsevier, Amsterdam.

Abstract: http://www.sciencedirect.com/science/book/9780444527714

Harada T, Enomoto A, Boorman GA, Maronpot RR. 1999. Liver and gallbladder. In: Pathology of the Mouse: Reference and Atlas (Maronpot RR, Boorman GA, Gaul BW, eds). Cache River Press, Vienna, IL, 119-183.

Abstract: http://www.cacheriverpress.com/books/pathmouse.htm

Hardisty JF, Brix AE. 2005. Comparative hepatic toxicity: Prechronic/chronic liver toxicity in rodents. Toxicol Pathol 33:35-40.

Full Text: http://tpx.sagepub.com/content/33/1/35.full.pdf

Haschek WM, Rousseaux CG, Wallig MA. 2010. Fundamentals of Toxicologic Pathology, 2nd ed. Academic Press, San Diego, 197-235.

Thoolen B, Maronpot RR, Harada T, Nyska A, Rousseaux C, Nolte T, Malarkey D, Kaufmann W, Kutter K, Deschl U, Nakae D, Gregson R, Winlove M, Brix A, Singl B, Belpoggi F, Ward JM. 2010. Hepatobiliary lesion nomenclature and diagnostic criteria for lesions in rats and mice (INHAND). Toxicol Pathol 38:5S-81S.

Full Text: http://tpx.sagepub.com/content/38/7_suppl/5S.full

All Images

Oval cell hyperplasia in a female Harlan Sprague-Dawley rat from a chronic study.

Oval cell hyperplasia in a female Harlan Sprague-Dawley rat from a chronic study.

Oval cell hyperplasia in a female Harlan Sprague-Dawley rat from a chronic study.

Oval cell hyperplasia in a female Harlan Sprague-Dawley rat from a chronic study.

Authors and Reviewers

Author

Robert R. Maronpot, DVM, MS, MPH, DACVP, DABT, FIATP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

John Cullen, VMD, PhD, DACVP, FIATP
Anatomic Pathology, Professor
North Carolina State University College of Veterinary Medicine
Raleigh, NC

David E. Malarkey DVM, PhD, DACVP, FIATP
Head, National Toxicology Program Pathology Group
Cellular and Molecular Pathology Branch
Division of the National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC